Is PEGylation of Drugs Associated with Hypersensitivity Reactions? An Analysis of the Italian National Spontaneous Adverse Drug Reaction Reporting System.

BACKGROUND AND OBJECTIVE: Evidence highlights the allergenic potential of PEGylated drugs because of the production of anti-polyethylene glycol immunoglobulins. We investigated the risk of hypersensitivity reactions of PEGylated drugs using the Italian spontaneous adverse drug reaction reporting system database. METHODS: We selected adverse drug reaction reports attributed to medicinal products containing PEGylated active substances and/or PEGylated liposomes from the Italian Spontaneous Reporting System in the period between its inception and March 2021. As comparators, we extracted adverse drug reaction reports of medicinal products containing the same non-PEGylated active substances and/or non-PEGylated liposomes (or compounds belonging to the same mechanistic class). A descriptive analysis of reports of hypersensitivity reactions was performed. Reporting rates and time to onset of hypersensitivity reactions were also calculated in the period between January 2009 and March 2021. As a measure of disproportionality, we calculated the reporting odds ratio. RESULTS: Overall, 3865 adverse drug reaction reports were related to PEGylated medicinal products and 11,961 to their non-PEGylated comparators. Around two-thirds of patients were female and reports mostly concerned patients aged between 46 and 64 years. The frequency of hypersensitivity reactions reporting was higher among PEGylated versus non-PEGylated medicinal products (11.7% vs 9.4%, p < 0.0001). The hypersensitivity reaction reporting rates were higher for PEGylated medicinal products versus non-PEGylated medicinal products, with reporting rate ratios that ranged from 1.4 (95% confidence interval 0.8-2.5) for pegfilgrastim versus filgrastim to 20.0 (95% confidence interval 2.8-143.5) for peginterferon alpha-2a versus interferon alpha-2a. The median time to onset of hypersensitivity reactions was 10 days (interquartile range: 0-61) for PEGylated medicinal products, and 36 days (interquartile range: 3-216) for non-PEGylated comparators. Statistically significant reporting odds ratios were observed when comparing the reporting of hypersensitivity reactions for PEGylated versus non-PEGylated medicinal products (reporting odds ratio: 1.3; 95% confidence interval 1.1-1.4). However, when using all other drugs as comparators, the disproportionality analysis showed no association with hypersensitivity reactions for PEGylated nor non-PEGylated medicinal products, thus suggesting that many other triggers of drug-induced hypersensitivity reactions play a major role. CONCLUSIONS: The findings of this analysis of the Italian spontaneous adverse drug reaction database suggest a potential involvement for PEGylation in triggering drug-related hypersensitivity reactions, especially clinically relevant reactions. However, when comparing both PEGylated and non-PEGylated drugs under study to all other drugs no disproportionate reporting of hypersensitivity reactions was observed, probably due to a masking effect owing to the presence in the same database of other medicinal products increasing the threshold required to highlight a safety signal when the entire database is used as a reference.

SARS-CoV-2 vaccination in androgen sensitive phenotypes - A study on associated factors for SARS-CoV-2 vaccination and its adverse effects among androgenetic alopecia and benign prostate hyperplasia patients.

Background: Androgen sensitivity, which was established as the leading etiology of androgenetic alopecia (AGA) and benign prostatic hyperplasia (BPH), plays an important role in SARS-CoV-2 infection. Vaccination is essential for AGA and BPH patients in view of the high risk from SARS-CoV-2 infection. Purpose: We aimed to investigate the associated factors for SARS-CoV-2 vaccination and its side effects in populations with AGA and BPH. Method: We collected the data on SARS-CoV-2 vaccination and adverse reactions of male AGA and BPH patients visited the outpatient of Xiangya hospital by telephone and web-based questionnaires. Vaccination rate and adverse reactions were compared by different vaccine types and use of anti-androgen therapy. Result: A total of 457 AGA patients and 397 BPH patients were recruited in this study. Among which, 92.8% AGA patients and 61.0% BPH patients had at least the first dose of SARS-CoV-2 vaccination (p < 0.001). Having comorbidities and use of anti-androgen therapy increased the risk of un-vaccination among AGA by 2.875 and 3.729 times, respectively (p < 0.001). Around 31.1% AGA patients and 9.5% BPH patients presented adverse reactions, which were mostly mild. Anti-androgen therapy increased the inclination of injection site pain after vaccination (18.7% vs 11.9%; OR: 1.708, 95% CI: 1.088-2.683, p = 0.019). Conclusion: Co-existence of other systemic diseases and anti-androgen therapy were the limiting factors for SARS-CoV-2 unvaccination, especially in AGA patients. The importance of SARS-CoV-2 vaccines should be strengthened and popularized in androgen sensitive phenotypes.

A cross-sectional study of COVID-19 vaccination patterns among patients with epilepsy in Hong Kong.

OBJECTIVE: As Hong Kong faced the 5th wave of the COVID-19 pandemic, the facilitators and hurdles toward effective vaccination is important for healthcare professionals to understand the vaccination gap among patients with epilepsy. METHODS: A cross-sectional, pragmatic study of COVID-19 vaccination was performed at a tertiary epilepsy center with regards to patterns of vaccination and any unusually high rate of adverse events. Patients having recent visits at the epilepsy center (4 months) had their anonymized electronic linkage records examined 12 months after the inception of vaccination program for types of vaccines, seizure demographics, and adverse events following immunization (AEFI). RESULTS: A total of 200 patients with epilepsy and their anonymized data were analyzed. The vaccine uptake was approximately 60% of that of the general population. Twice as many patients with epilepsy chose to receive mRNA vaccine as compared with inactivated vaccine. The proportion of patients who kept up-to-date with all available dosing was 7%. Patients with epilepsy with genetic etiology were least likely to receive vaccination (13/38, 34%, P = .02). There was no unreasonably high rate of unacceptable side effects after vaccination among patients with epilepsy. Only 3 patients reported worsening of seizures without meeting the criteria for AEFI. Refractory epilepsy, allergy to antiseizure medications and elder age (≥65) did not confer any significant difference in vaccination patterns or adverse effects. SIGNIFICANCE: A vaccination gap exists among epilepsy patients which calls for actionable strategies for improving vaccine uptake, including education and outreach programs.

Post-COVID-19 vaccination IgA vasculitis in an adult.

Leukocytoclastic vasculitis has been reported in the setting of COVID-19 infection and post-COVID-19 vaccination. We report a case of IgA vasculitis (IgAV) post-COVID-19 vaccination, with immunoglobulin A (IgA) immune deposits in the skin and renal involvement. SARS-CoV spike protein immunohistochemical staining was negative. IgAV with skin and renal involvement is a potential reaction to COVID-19 vaccination.

Inherent Dangers of Using Non-US Food and Drug Administration-Approved Substances of Abuse.

Use of US Food and Drug Administration-approved substances of abuse has innate risks due to pharmacologic and pharmacokinetic properties of the medications, but the risk when using nonapproved drug products is much greater. Unbeknownst to the user, the dose of active ingredients in substances of abuse can vary substantially between different products because of manufacturing practices or improper storage. Even naturally occurring substances of abuse can have extensive dosage variability because of effects of the growing season and conditions, or differences in harvesting, storage, or manufacture of the finished products. Many illicit substances are adulterated, to make up for intentional underdosing or to enhance the effect of the intended active ingredient. These adulterants can be dangerous and produce direct cardiovascular, neurologic, hematologic, or dermatologic reactions or obscure adverse effects. Finally, an illicit substance can be contaminated or substituted for another one during its manufacture, leading to differences in adverse events, adverse event severity, or the drug interaction profile. Substances can be contaminated with microbes that induce infections or heavy metals that can damage organs or cause cancer. This milieu of undisclosed substances can also induce drug interactions. For reasons that are discussed, individuals who use substances of abuse are at increased risk of morbidity or mortality if they develop coronavirus disease 2019. Health professionals who treat patients with acute, urgent events associated with substances of abuse, or those treating the chronic manifestations of addiction, need to appreciate the complex and variable composition of substances of abuse and their potential health effects.